2011 Genitourinary Cancers Symposium
ORLANDO — Intermittent androgen suppression therapy
yielded similar OS outcomes as continuous androgen deprivation in a cohort of
men with localized prostate cancer who had received radical radiotherapy,
according to findings presented here.
Laurence Klotz, MD, chief of urology at
Sunnybrook Health Sciences Center, and professor of surgery at the University
of Toronto, said intermittent therapy was delivered in 8-month cycles and was
restarted when PSA levels were more than 10 ng/mL during nontreatment times.
There were 690 patients in the intermittent therapy arm
and 696 patients in the continuous
androgen deprivation therapy arm. The median duration of
follow-up was 6.9 years.
“The median OS was 8.8 years in the intermittent
therapy arm and 9.1 years in the continuous therapy arm,” Klotz said.
“Intermittent therapy was noninferior to continuous therapy with regard to
OS. Moving forward, this should be the standard of care for these
There were 268 deaths in the intermittent therapy arm
and 256 deaths in the continuous therapy arm.
There were 122 disease-related deaths in the
intermittent arm vs. 97 in the androgen therapy arm. “The difference in
disease-specific mortality was also nonsignificant,” Klotz said, adding
that there were fewer deaths unrelated to disease in the intermittent therapy
arm, 134 vs. 146.
He also reported on time to castration-resistant
disease. “The curves for castration-resistant disease came together at
around 10 years,” he said. “There was not much difference between the
Apart from reduced incidence of hot flashes in the
intermittent therapy group, no differences in adverse events, including
myocardial events or osteoporotic fractures, were observed between the two
The primary endpoint was OS. Secondary endpoints
included time to hormone refractory state, quality of life, HDL and LDL
cholesterol levels, duration of treatment and nontreatment intervals, time to
testosterone and potency recovery, according to Klotz.
The aim of the trial was to determine whether
intermittent androgen suppression could improve survival and quality-of-life
outcomes in men with PSA recurrence, which was defined as more than 3 ng/ml,
more than a year after radical radiotherapy.
The median number of 8-month cycles completed by the
intermittent therapy patients was two (range, 1-9).
An independent review committee recommended halting the
trial when prespecified noninferiority boundaries were crossed.
Initial enrollment occurred in January 1999, and the
most recent follow-up was conducted in October. Patients were stratified by
time since radical radiation, initial PSA, prior radical prostatectomy and
prior androgen deprivation therapy.
For more information:
Disclosure: Dr. Klotz reports no relevant financial disclosures.
Intermittent therapy has been a talking point for a while now. This was
the largest trial by far testing this strategy. It is important because it
unequivocally shows that the OS is identical between intermittent and
continuous approaches. This will be the definitive trial that I cite when
discussing this approach.
One possible area of concern, however, is compliance. Of course,
patients are compliant during treatment times, but we also have to be careful
of what is happening while they are being monitored. This requires focus on the
part of the patient and the clinician.
Another caveat is that we should take note of the difference between OS
and time to castration-resistant disease. The disease will be recurrent, but
this study shows that it can be controlled with intermittent therapy.
A final point of note that was not reported on but that needs to be
discussed is the cost-savings with intermittent treatment. It is a simple
equation: Less frequent treatment and less medication translate to less money
Oliver Sartor, MD
Medical Director, Tulane
Cancer Center; Director, Prostate Cancer Program
Disclosure: Dr. Sartor reports no relevant financial disclosures.
Intermittent androgen deprivation appears to be an acceptable
alternative to continuous androgen deprivation for men with a rising PSA after
definitive local therapy with radiation or a prostatectomy followed by
This study builds on several smaller studies and
provides definitive evidence for the safety of intermittent androgen
deprivation for men with PSA recurrence. Quality of life assessment, a
secondary endpoint of the study will be reported at a future time. However,
clinical experience suggests that patients off androgen deprivation have an
improved sense of well being making intermittent androgen deprivation the
preferred means of administering hormonal therapy in this population of men.
- Mark Stein, MD
HemOnc Today Editorial Board Member
Disclosure: Dr. Stein reports no relevant financial disclosures.